Differentiating Allergic Reactions vs Bradykinin-Induced Angioedema: A Guide for PLAB 2

Practice a case with the AI patient 🤖

Angioedema is a common emergency presentation in the UK, and PLAB 2 candidates must clearly differentiate between histamine-mediated (allergic) and bradykinin-mediated (non-allergic) causes to provide safe and effective management.

✅ Key Differences at a Glance

Feature	Allergic Reaction (Histamine-Mediated)	Bradykinin-Mediated Angioedema (e.g., ACE inhibitor–induced)
Cause	IgE-mediated hypersensitivity (e.g. food, drug, insect sting)	Bradykinin accumulation due to ACE inhibitors
Onset	Rapid — usually within minutes to 1 hour after exposure	Variable — can occur anytime, even months or years after starting ACE inhibitor
Symptoms	Urticaria, flushing, itching, wheeze, hypotension, stridor, GI symptoms	Isolated swelling (often face, lips, tongue); no rash, no itching
Airway risk	High if tongue, throat, or larynx is involved	High if tongue or upper airway involved
Biphasic reaction	Possible — second reaction after 4–12 hours	Not typical — no biphasic reaction seen
Family history	Not usually relevant	May be relevant in hereditary angioedema (HAE)
Response to adrenaline/steroids/antihistamines	Typically good	Minimal or no response
Specific treatment	Adrenaline, antihistamines, steroids	Stop ACE inhibitor, consider Icatibant if severe
Recurrence	Avoid allergen to prevent recurrence	Will recur if ACE inhibitor is continued

🔍 Severity: How to Identify Risk

Allergic Reaction – Signs of Severe (Anaphylaxis):

• Rapid onset swelling of tongue/lips/throat

• Difficulty breathing, wheezing

• Hypotension, collapse

• Urticaria, flushing, or vomiting

→ Treat immediately as anaphylaxis→ Observe for biphasic reaction up to 12–24 hours if moderate to severe

Bradykinin-Mediated Angioedema – Severity Clues:

• Often presents as isolated swelling (esp. face/tongue)

• No itching, rash, or flushing

• May progress slowly but can compromise airway

• No biphasic pattern, but airway swelling can worsen

💊 Treatment Summary

🟢 Allergic/Anaphylactic Angioedema (Histamine-Mediated)

1. Adrenaline 0.5 mg IM – first-line

2. Chlorphenamine 10 mg IV/IM – antihistamine

3. Hydrocortisone 200 mg IV – steroid

4. Oxygen + Fluids as needed

5. Observe for 6–12 hrs if moderate to severe

🔴 Bradykinin-Mediated Angioedema (e.g., Ramipril-induced)

1. Stop ACE inhibitor permanently

2. Adrenaline/steroids/antihistamines often ineffective – but may be given initially if unsure

3. Airway support is critical – escalate early if swelling is progressing

4. Icatibant (if available) – bradykinin B2 receptor antagonist

5. Monitor closely if airway involved; no need to observe for biphasic reaction if stable

📘 PLAB 2 Tip

❗If a patient on ramipril develops sudden tongue swelling but no rash or itch, think bradykinin-angioedema — stop ACE inhibitor immediately and assess airway.

Use ICE (Ideas, Concerns, Expectations) to explore the patient's understanding, and always safety-net in allergic cases due to possible biphasic reaction.

🧠 Takeaway for PLAB 2 OSCE:

• Always assess airway risk.

• Know the difference in pathophysiology to guide management.

• Document clearly and escalate early when needed.